AAN指南PPT治疗痛性糖尿病神经病课件.ppt

TreatmentofPainfulDiabeticNeuropathy ReportoftheAmericanAcademyofNeurology theAmericanAssociationofNeuromuscularandElectrodiagnosticMedicine andtheAmericanAcademyofPhysicalMedicineandRehabilitation VeraBril MD FRCP C JohnEngland MD FAAN GaryM Franklin MD MPH FAAN MiroslavBackonja MD JeffreyCohen MD FAAN DavidDelToro MD EvaFeldman MD PhD FAAN DonaldJ Iverson MD FAAN BrucePerkins MD FRCP C MPH JamesW Russell MD MS FRPC DouglasZochodne MD Ifyouhavequestions comments orfeedbackregardingthisslidepresentation orwouldliketomodifythecontentsforpresentationinalecture pleasecontactguidelines PresentationObjectives Topresentanalysisoftheefficacyofpharmacologicandnonpharmacologictreatmentstoreducepainandimprovephysicalfunctionandqualityoflife QOL inpatientswithpainfuldiabeticneuropathy PDN Topresentevidence basedrecommendations Overview BackgroundGapsincareAmericanAcademyofNeurology AAN guidelineprocessAnalysisofevidence conclusions recommendationsRecommendationsforfutureresearch Background Diabeticsensorimotorpolyneuropathyrepresentsadiffusesymmetricandlength dependentinjurytoperipheralnervesthathasmajorimplicationsforQOL morbidity andcostfromapublichealthperspective 1 2PDNaffects16 ofpatientswithdiabetes itisfrequentlyunreported 12 5 andmorefrequentlyuntreated 39 3PDNpresentsanongoingmanagementproblemforpatients caregivers andphysicians Manytreatmentoptionsareavailable andarationalapproachtotreatingpatientswithPDNrequiresanunderstandingoftheevidenceforeachintervention ThisguidelineaddressestheefficacyofpharmacologicandnonpharmacologictreatmentstoreducepainandimprovephysicalfunctionandQOLinpatientswithPDN Background cont PharmacologicAgents Anticonvulsants antidepressants opioids antiarrhythmics cannabinoids aldosereductaseinhibitors proteinkinaseCbetainhibitors antioxidants lipoicacid transketolaseactivators thiaminesandallithiamines topicalmedications analgesicpatches anestheticpatches capsaicincream clonidine andothersNonpharmacologicModalities Infraredtherapy shoemagnets exercise acupuncture externalstimulation transcutaneouselectricalnervestimulation spinalcordstimulation biofeedbackandbehavioraltherapy surgicaldecompression andintrathecalbaclofen GapsinCare Thechroniceffectofdrugtherapiesisnotknown howlongtotreat whenorwhethertowithdrawtreatment Thereisaninsufficientnumberofcomparativestudiesamonghigh qualitystudies mostwereClassIIorlower Thereisnouniformityinhowtomeasurepain QOL andfunctionacrossthestudiesexamined Lackofcosteffectivenessisapparentinallofthestudies Estimatednumbersneededtotreatareavailable butnumbersneededtoharmarenotavailable TheAANclassifiesstudiesbyqualityoftheevidence notbycost GapsinCare cont Practitionersdon tidentifypainenoughinperipheralneuropathyordiabeticneuropathy Patientswithdiabetesoftenaren tawarethatnervepainisasymptom Mostneuropathytherapiestreatpainbutnotnumbness ThereisalackofattentiontoPDNasadiseaseentity AANGuidelineProcess ClinicalQuestionEvidenceConclusionsRecommendations ClinicalQuestions Thefirststepindevelopingguidelinesistoclearlyformulatequestionstobeanswered Questionsaddressareasofcontroversy confusion orvariationinpractice Questionsmustbeanswerablewithdatafromtheliterature Answeringthequestionmusthavethepotentialtoimprovecare patientoutcomes LiteratureSearch Review Rigorous Comprehensive Transparent AANClassificationofEvidence AllstudiesratedClassI II III orIVFivedifferentclassificationsystems TherapeuticRandomization control blindingDiagnosticComparisontogoldstandardPrognosticScreeningCausation AANLevelofRecommendations A Establishedaseffective ineffectiveorharmful orestablishedasuseful predictiveornotuseful predictive forthegivenconditioninthespecifiedpopulation B Probablyeffective ineffectiveorharmful orprobablyuseful predictiveornotuseful predictive forthegivenconditioninthespecifiedpopulation C Possiblyeffective ineffectiveorharmful orpossiblyuseful predictiveornotuseful predictive forthegivenconditioninthespecifiedpopulation U Datainadequateorconflicting givencurrentknowledge treatment test predictor isunproven Notethatrecommendationscanbepositiveornegative TranslatingClasstoRecommendations A RequiresatleasttwoconsistentClassIstudies B RequiresatleastoneClassIstudyortwoconsistentClassIIstudies C RequiresatleastoneClassIIstudyortwoconsistentClassIIIstudies U StudiesnotmeetingcriteriaforClassIthroughClassIII TranslatingClasstoRecommendations cont Inexceptionalcases oneconvincingClassIstudymaysufficeforan A recommendationif1 allcriteriaaremet 2 themagnitudeofeffectislarge relativerateimprovedoutcome 5andthelowerlimitoftheconfidenceintervalis 2 ApplyingThisProcesstotheIssue Wewillnowturnourattentiontotheguidelines ClinicalQuestions 1 InpatientswithPDN whatistheefficacyofpharmacologicagentstoreducepainandimprovephysicalfunctionandQOL InpatientswithPDN whatistheefficacyofnonpharmacologicmodalitiestoreducepainandimprovephysicalfunctionandQOL Methods MEDLINEandEMBASE1960toAugust2008Relevant fullypublished peer reviewedarticlesMeSHterm diabeticneuropathies anditstextwordsynonymsandkeywordsforthetherapeuticinterventionsofinterest seepublishedguidelineforfulllistofterms Methods cont Atleasttwoauthorsreviewedeacharticleforinclusion Riskofbiaswasdeterminedusingtheclassificationofevidenceforeachstudy ClassesI IV Strengthofpracticerecommendationswerelinkeddirectlytolevelsofevidence LevelsA B C andU Conflictsofinterestweredisclosed LiteratureReview Inclusioncriteria ArticlesdealingwithPDN describingtheinterventionclearly reportingstudycompletionrates definingtheoutcomemeasuresclearlyExclusioncriteria Casereportsandreviewpapers AANClassificationofEvidenceforTherapeuticIntervention ClassI Arandomized controlledclinicaltrialoftheinterventionofinterestwithmaskedorobjectiveoutcomeassessment inarepresentativepopulation Relevantbaselinecharacteristicsarepresentedandsubstantiallyequivalentamongtreatmentgroupsorthereisappropriatestatisticaladjustmentfordifferences Thefollowingarealsorequired concealedallocationprimaryoutcome s clearlydefinedexclusion inclusioncriteriaclearlydefined AANClassificationofEvidenceforTherapeuticIntervention cont adequateaccountingfordrop outs withatleast80 ofenrolledsubjectscompletingthestudy andcross overswithnumberssufficientlylowtohaveminimalpotentialforbias Fornoninferiorityorequivalencetrialsclaimingtoproveefficacyforoneorbothdrugs thefollowingarealsorequired Theauthorsexplicitlystatetheclinicallymeaningfuldifferencetobeexcludedbydefiningthethresholdforequivalenceornoninferiority Thestandardtreatmentusedinthestudyissubstantiallysimilartothatusedinpreviousstudiesestablishingefficacyofthestandardtreatment e g foradrug themodeofadministration doseanddosageadjustmentsaresimilartothosepreviouslyshowntobeeffective Theinclusionandexclusioncriteriaforpatientselectionandtheoutcomesofpatientsonthestandardtreatmentarecomparabletothoseofpreviousstudiesestablishingefficacyofthestandardtreatment Theinterpretationoftheresultsofthestudyisbaseduponaperprotocolanalysisthattakesintoaccountdropoutsorcrossovers AANClassificationofEvidenceforTherapeuticIntervention cont ClassII Arandomizedcontrolledclinicaltrialoftheinterventionofinterestinarepresentativepopulationwithmaskedorobjectiveoutcomeassessmentthatlacksonecriteriaa eaboveoraprospectivematchedcohortstudywithmaskedorobjectiveoutcomeassessmentinarepresentativepopulationthatmeetsb eabove Relevantbaselinecharacteristicsarepresentedandsubstantiallyequivalentamongtreatmentgroupsorthereisappropriatestatisticaladjustmentfordifferences AANClassificationofEvidenceforTherapeuticIntervention cont ClassIII Allothercontrolledtrials includingwell definednaturalhistorycontrolsorpatientsservingasowncontrols inarepresentativepopulation whereoutcomeisindependentlyassessed orindependentlyderivedbyobjectiveoutcomemeasurement ClassIV StudiesnotmeetingClassI IIorIIIcriteriaincludingconsensusorexpertopinion Notethatnumbers1 3inClassI item5arerequiredforClassIIinequivalencetrials Ifanyoneofthethreearemissing theclassisautomaticallydowngradedtoClassIII AnalysisofEvidence Question1 InpatientswithPDN whatistheefficacyofpharmacologicagentstoreducepainandimprovephysicalfunctionandQOL Conclusions Recommendation Conclusions BasedonconsistentClassIevidence pregabalinisestablishedaseffectiveinlesseningthepainofPDN PregabalinalsoimprovesQOLandlessenssleepinterference thoughtheeffectsizeissmall Recommendation Ifclinicallyappropriate pregabalinshouldbeofferedforthetreatmentofPDN LevelA 2020 1 30 27 可编辑 Conclusions Recommendation Conclusions Basedon1ClassIstudy gabapentinisprobablyeffectiveinlesseningthepainofPDN Basedon2ClassIIstudies sodiumvalproateisprobablyeffectiveintreatingPDN Recommendation GabapentinandsodiumvalproateshouldbeconsideredforthetreatmentofPDN LevelB Conclusion Recommendation Conclusion ThereisconflictingClassIIIevidencefortheeffectivenessoftopiramateintreatingPDN Recommendation ThereisinsufficientevidencetosupportorrefutetheuseoftopiramateforthetreatmentofPDN LevelU Conclusions Recommendation Conclusions LamotrigineisprobablynoteffectiveintreatingPDN BasedonClassIIevidence oxcarbazepineisprobablynoteffectiveintreatingPDN BasedonClassIIIevidence lacosamideispossiblynoteffectiveintreatingPDN Thedegreeofpainreliefaffordedbyanticonvulsantagentsisnotassociatedwithimprovedphysicalfunction Recommendation Oxcarbazepine lamotrigine andlacosamideshouldprobablynotbeconsideredforthetreatmentofPDN LevelB ClinicalContext AlthoughsodiumvalproatemaybeeffectiveintreatingPDN itispotentiallyteratogenicandshouldbeavoidedindiabeticwomenofchildbearingage Duetopotentialadverseeffectssuchasweightgainandpotentialworseningofglycemiccontrol thisdrugisunlikelytobethefirsttreatmentchoiceforPDN Conclusions Recommendations Conclusions Basedon3ClassIand5ClassIIstudies theantidepressantsamitriptyline venlafaxine andduloxetineareprobablyeffectiveinlesseningthepainofPDN VenlafaxineandduloxetinealsoimproveQOL Venlafaxineissuperiortoplaceboinrelievingpainwhenaddedtogabapentin Recommendations Amitriptyline venlafaxine andduloxetineshouldbeconsideredforthetreatmentofPDN LevelB Dataareinsufficienttorecommendoneoftheseagentsovertheothers Venlafaxinemaybeaddedtogabapentinforabetterresponse LevelC Conclusion Recommendation Conclusion Thereisinsufficientevidencetodeterminewhetherdesipramine imipramine fluoxetine orthecombinationofnortriptylineandfluphenazineareeffectiveforthetreatmentofPDN Recommendation Thereisinsufficientevidencetosupportorrefutetheuseofdesipramine imipramine fluoxetine orthecombinationofnortriptylineandfluphenazineinthetreatmentofPDN LevelU Conclusions Recommendation Conclusions BasedononeClassIstudy dextromethorphanisprobablyeffectiveinlesseningthepainofPDNandimprovingQOL BasedonClassIIevidence morphinesulphate tramadol andoxycodonecontrolled releaseareprobablyeffectiveinlesseningthepainofPDN Dextromethorphan tramadol andoxycodonecontrolled releasehavemoderateeffectsizes reducingpainby27 comparedwithplacebo Recommendation Dextromethorphan morphinesulphate tramadol andoxycodoneshouldbeconsideredforthetreatmentofPDN LevelB Dataareinsufficienttorecommendoneagentovertheother ClinicalContext Theuseofopioidsforchronicnonmalignantpainhasgainedcredenceoverthelastdecadeduetothestudiesreviewedinthisarticle Bothtramadolanddextromethorphanwereassociatedwithsubstantialadverseevents e g sedationin18 ontramadoland58 ondextromethorphan nauseain23 ontramadol andconstipationin21 ontramadol Theuseofopioidscanbeassociatedwiththedevelopmentofnovelpainsyndromessuchasreboundheadache Chronicuseofopioidsleadstotoleranceandfrequentescalationofdose Conclusions Recommendation Conclusions BasedonClassIandClassIIevidence capsaicincreamisprobablyeffectiveinlesseningthepainofPDN BasedonClassIevidence isosorbidedinitratesprayisprobablyeffectiveforthetreatmentofPDN Recommendation CapsaicinandisosorbidedinitratesprayshouldbeconsideredforthetreatmentofPDN LevelB Conclusions Recommendation Conclusions BasedonClassIIIstudies thereisinsufficientevidencetodetermineifIVlidocaineiseffectiveinlesseningthepainofPDN BasedonClassIIIevidence theLidodermpatchispossiblyeffectiveinlesseningthepainofPDN Recommendation TheLidodermpatchmaybeconsideredforthetreatmentofPDN LevelC Conclusions Recommendation Conclusions BasedonClassIevidence clonidineandpentoxifyllineareprobablynoteffectiveforthetreatmentofPDN Theevidencefortheeffectivenessofmexiletineiscontradictory however theonlyClassIstudyofthisagentindicatesthatmexiletineisprobablyineffectiveforthetreatmentofPDN Recommendation Clonidine pentoxifylline andmexiletineshouldprobablynotbeconsideredforthetreatmentofPDN LevelB Conclusion Recommendation Conclusion Thereisinsufficientevidencetodeterminewhethervitaminsand lipoicacidareeffectiveforthetreatmentofPDN Recommendation Thereisinsufficientevidencetosupportorrefutetheusefulnessofvitaminsand lipoicacidinthetreatmentofPDN LevelU ClinicalContext AlthoughcapsaicinhasbeeneffectiveinreducingpaininPDNclinicaltrials manypatientsareintolerantofthesideeffects mainlyburningpainoncontactwithwarm hotwaterorinhotweather AnalysisofEvidence Question2 InpatientswithPDN whatistheefficacyofnonpharmacologicmodalitiestoreducepainandimprovephysicalfunctionandQOL Conclusions Recommendations Conclusions BasedonaClassIstudy electricalstimulationisprobablyeffectiveinlesseningthepainofPDNandimprovingQOL BasedonsingleClassIstudies electromagneticfieldtreatment low intensitylasertreatment andReikitherapyareprobablynoteffectiveforthetreatmentofPDN Recommendations PercutaneouselectricalnervestimulationshouldbeconsideredforthetreatmentofPDN LevelB Electromagneticfieldtreatment low intensitylasertreatment andReikitherapyshouldprobablynotbeconsideredforthetreatmentofPDN LevelB Conclusion Recommendation Conclusion ThereisnotenoughevidencetosupportorexcludeabenefitofamitriptylinepluselectrotherapyintreatingPDN Recommendation EvidenceisinsufficienttosupportorrefutetheuseofamitriptylinepluselectrotherapyfortreatmentofPDN LevelU AnalysisofEvidence ComparisonStudies Studieswith2activetreatmentarmsandwithoutaplaceboarmwereconsideredseparatelyandgradedusingactivecontrolequivalencecriteria seeappendixe 2andtablee 6ofthepublishedguideline Weidentified6comparisonstudiesofagents gabapentintoamitriptyline 4venlafaxinetocarbamazepine nortriptyline fluphenazinetocarbamazepine capsaicintoamitriptyline andbenfotiamine cyanocobalaminwithconventionalvitaminB butdidnotfindevidencetorecommendoneovertheother 5 10Noneofthestudiesdefinedthethresholdforequivalenceornoninferiority ClinicalContext Itisnotablethattheplaceboeffectvariedfrom0 to50 painreductioninthesestudies AdjuvantanalgesicagentsaredrugsprimarilydevelopedforanindicationotherthanthetreatmentofPDN e g anticonvulsantsandantidepressants thathavebeenfoundtolessenpainwhengiventopatientswithPDN TheiruseinthetreatmentofPDNiscommon 11ThepanelrecognizesthatPDNisachronicdiseaseandthattherearenodataontheefficacyofthechronicuseofanytreatment asmosttrialshavedurationsof2 20weeks Itisimportanttonotethattheevidenceislimited thedegreeofeffectivenesscanbeminor thesideeffectscanbeintolerable theimpactonimprovingphysicalfunctionislimited andthecostishigh particularlyfornovelagents FutureResearch Aformalizedprocessforratingpainscalesforuseinallclinicaltrialsshouldbedeveloped ClinicaltrialsshouldbeexpandedtoincludeeffectsonQOLandphysicalfunctionwhenevaluatingefficacyofnewinterventionsforPDN themeasuresshouldbestandardized Futureclinicaltrialsshouldincludehead to headcomparisonsofdifferentmedicationsandcombinationsofmedications BecausePDNisachronicdisease trialsoflongerdurationshouldbedone Standardmetricsforsideeffectstoqualifyeffectsizesofinterventionsneedtobedeveloped Cost effectivenessstudiesofdifferenttreatmentsshouldbedone Themechanismofactionofelectricalstimulationisunknown abetterunderstandingofitsrole modeofapplication andotheraspectsofitsuseshouldbestudied References BoultonAJ VinikAI ArezzoJC etal Diabet